The ascidian, Ecteinascidia turbinata, is a colonial tunicate from the family Perophoridae, found in the Caribbean and Mediterranean Seas. As an important component of the benthic ecology of the Caribbean mangroves, it has been the subject of various studies examining settlement, species succession and larval behaviour.
In the 1960's interest in this species was heightened when an extract of the animal was found to have cytotoxic properties. It was not until the 1980's that the compounds conferring these properties, the ecteinascidins, were identified and characterised. One of these compounds, ET-743, with remarkable cytotoxic acitvity, is presently in clinical trials for the treament of cancer.
Nearly 20 years on, little is known about the production of these important secondary metabolites or what function, if any, they play in the animal.
Bioactive secondary metabolites are found in many marine invertebrates; especially sponges, molluscs, bryozoans and ascidians, and new compounds are constantly being described.
Marine invertebrate secondary metabolites encompass a wide range of chemical types including macrolides, terpenes, steroids, peptides and alkaloids, frequently with complex structures. As yet, there is little direct evidence for the function these compounds may have in their hosts, although relevant laboratory and field-based studies are beginning to address this area. Some investigations support a role in chemical defense, as anti-fouling, anti-infective or anti-predation agents. Many sponges are known to produce noxious chemicals and feeding studies have indicated that these compounds appear to confer protection against predators. Marine larvae of chemically defended adults also possess anti-predatory compounds.
As soft bodied, sessile marine invertebrates, adult ascidians are especially susceptible to predation, and to fouling of their external surfaces. The production of potentially defensive secondary metabolites appears widespread among certain groups of ascidians. Feeding studies using crab and fish predators have indicated that in some ascidians these metabolites confer antipredatory protection. Many ascidians also produce large, conspicuous larvae, which develop in a brood pouch. These larvae are released in daylight hours, so they can search for optimal settlement sites, and have a short swimming phase. This strategy leaves the larvae exposed to predators and it has been suggested that selection by these predators may favour the evolution of distasteful larvae. Indeed many such larvae may be chemically defended, being unpalatable to predators when presented in feeding experiments.
There is little known of the mechanisms of production of secondary metabolites in many species. There is evidence to support the theory that symbionts (especially bacterial ones) within the invertebrate host produce at least some of these secondary metabolites, either on their own, or in conjunction with their host. This idea is based on the fact that some secondary metabolites show close similarities to compounds produced by bacteria. Although the evidence to support this theory is still limited, and in some cases the picture is likely to be very complex with no clear unique source for a metabolite, certain studies have added experimental support to the argument.
Although there are many secondary metabolite-producing ascidians, there are very few studies on the presence of microorganisms specifically associated with ascidians, as epi- or endobionts. However, there are now many descriptions of symbiotic associations between bacteria and other marine invertebrate hosts, for example in sponges, molluscs, bryozoans and echinoderms.
Despite the increasing number of studies, the association between chemical defense, secondary metabolites and bacterial symbiosis, is not understood.
Ecteinascidia turbinata is the source of natural product ET-743 which is being developed as antitumoral agent. The cytotoxic compound is extracted from the ascidian which is obtained by aquaculture. Due to the life cycle of the Ecteinascidia turbinata this is a time consuming and laborious process.
Chemical routes to ET-743 are the total synthesis, and the hemisynthesis from cyanosafracin B obtained by fermentation. Although these processes provide alternatives to the natural sources of ecteinascidins, they still involve numerous chemical steps and are expensive.
There is a need to provide new sources of the ecteinascidin compounds which are not subject to the difficulties described above.